Biology subjects

Ristoratore, F.

Publications and source records attributed to Ristoratore, F..

4 recordsLinked to original sources

bioRxiv2026

Fine-tuning neuron number: Lzts as a key regulator of neurogenesis and cell proliferation in Ciona

How progenitor mitotic timing is coupled to the number of neurons in a nervous system remains poorly understood, in part because most model systems have large, variable progenitor pools that obscure this relationship. The non-vertebrate chordate Ciona robusta offers a tractable alternative: its larval nervous system arises from an invariant lineage, including four Bipolar Tail Neurons (BTNs) that are reproducibly generated from the caudal neural plate border. Here we investigate the developmental function of the single Ciona ortholog belonging to the leucine zipper tumor suppressor (Lzts) gene family, whose vertebrate members are implicated in cell-cycle regulation and tumor suppression. In Ciona, Lzts is expressed in several embryonic tissues, including differentiating BTNs. Tissue-specific CRISPR/Cas9 knockout of Lzts in the BTN lineage produced supernumerary BTNs, without expanding the embryonic Neurog+ domain, indicating that Lzts acts downstream of BTN specification to limit neuron number. Lzts1 promotes Cdk1 activity via stabilization of Cdc25C, co-expression of Ciona Cdc25C or a non-phosphorylatable Cdk1/2/3 mutant rescued normal BTN number in Lzts crispants, proving the existence of an ancestral Lzts-Cdc25-Cdk1 circuit controlling neural cell cycle. These findings establish Ciona Lzts as a regulator of mitotic tempo determining the BTN number and suggest that this cell-cycle regulatory axis links proliferation to neurogenesis across chordates in vivo.

developmental biology↗

bioRxiv2026

Developmental genetic response of the zooplanktonic tunicate Oikopleura dioica to marine noise pollution.

BackgroundAnthropogenic noise is an emerging threat to marine ecosystems, yet its effects on marine invertebrates, particularly zooplanktonic species, remain poorly understood. Despite increasing evidence of behavioral and physiological impacts in invertebrates, the effects of noise on embryonic development and the molecular mechanisms underlying acoustic responses remain largely unexplored. Here, to address this gap, we investigated the impact of high-intensity underwater noise exposure on embryogenesis of the appendicularian tunicate Oikopleura dioica, a cosmopolitan zooplanktonic tunicate that plays important ecological roles in marine trophic webs and carbon cycling. Under lab-controlled conditions, we examined the effects of experimental noise exposure on early embryogenesis at both morphological and transcriptomic levels using RNA-seq in 8-cell (8c) and early tailbud (ETB) stages. ResultsNoise exposure produced no significant increase in embryo malformations compared to non-exposed controls, indicating substantial phenotypic resilience under laboratory conditions. Interestingly, transcriptomic analyses revealed a rapid molecular response of 70 differentially expressed genes (DEG) already detectable after only 30 minutes of exposure at the 8-cell stage, which became markedly amplified with 700 DEGs by the ETB stage. Together, differential expression, GO enrichment, and co-expression network analyses identified coordinated regulation of processes associated with membrane homeostasis, pyrimidine/CTP metabolism, extracellular matrix organization, cytoskeletal architecture, RNA regulation, translational control, proteostasis, mitochondrial metabolism, and developmental pathways. Importantly, both developmental stages precede the formation of differentiated mechanosensory structures, suggesting that the observed responses are unlikely to reflect conventional sound perception. ConclusionsThese findings provide the first molecular characterization of noise effects during O. dioica embryogenesis and reveal an unexpected molecular sensitivity of O. dioica embryos to underwater noise despite preserved morphological development. The transcriptional signatures support a mechanobiological framework in which acoustic exposure may directly perturb cellular mechanical homeostasis through membrane-and cytoskeleton-associated processes, triggering compensatory stress-adaptation responses involving proteostasis, RNA regulation, and metabolic reprogramming. Together, these findings establish O. dioica as a valuable emerging model for investigating the developmental and evolutionary consequences of acoustic pollution in marine ecosystems.

developmental biology↗

bioRxiv2021

Identification of LINE retrotransposons and long non-coding RNAs expressed in the octopus brain

BackgroundTransposable elements (TEs) widely contributed to the evolution of genomes allowing genomic innovations, generating germinal and somatic heterogeneity and giving birth to long non-coding RNAs (lncRNAs). These features have been associated to the evolution, functioning and complexity of the nervous system at such a level that somatic retrotransposition of long interspersed element (LINE) L1 has been proposed to be associated to human cognition. Among invertebrates, octopuses are fascinating animals whose nervous system reaches a high level of complexity achieving sophisticated cognitive abilities. The sequencing of the genome of the Octopus bimaculoides revealed a striking expansion of TEs which were proposed to have contributed to the evolution of its complex nervous system. We recently found a similar expansion also in the genome of Octopus vulgaris. However a specific search for the existence of full-length transpositionally competent TEs has not been performed in this genus. ResultsHere we report the identification of LINE elements competent for retrotransposition in Octopus vulgaris and Octopus bimaculoides and show evidence suggesting that they might be active driving germline polymorphisms among individuals and somatic polymorphisms in the brain. Transcription and translation measured for one of these elements resulted in specific signals in neurons belonging to areas associated with behavioral plasticity. We also report the transcription of thousands of lncRNAs and the pervasive inclusion of TE fragments in the transcriptomes of both Octopus species, further testifying the crucial activity of TEs in the evolution of the octopus genomes. ConclusionsThe neural transcriptome of the octopus shows the transcription of thousands of putative lncRNAs and of a full lenght LINE element belonging to the RTE class. We speculate that a convergent evolutionary process involving retrotransposons activity in the brain has been important for the evolution of sophisticated cognitive abilities in this genus.

genomics↗

bioRxiv2019

A cis-regulatory change underlying the motor neuron-specific loss of terminal selector gene expression in immotile tunicate larvae

The evolutionary history of animal body plans cannot be fully reconstructed without considering the roles of both novelties and losses. Some of the more remarkable examples of massively parallel evolutionary losses in animals comes from many species in the tunicate genus Molgula that have independently lost the swimming larva and instead develop as tail-less, immotile larvae that bypass the period of swimming and dispersal observed in other tunicates, marine invertebrate chordates that alternate between motile larval and sessile adult life cycle stages. The larvae of Molgula occulta and other tail-less species do not fully develop structures that are essential for swimming behavior, including notochord, tail muscles, and otolith, and loss-of-function mutations have been identified in various genes required for the differentiation of these tissues. However, little is known about the extent of development of the larval nervous system in M. occulta. While differentiated neurons might in principle be entirely dispensable to the non-swimming larva, the adult has a fully functional nervous system like any other tunicate. To further investigate this conundrum, we studied the specification and patterning of the M. occulta Motor Ganglion, which is the key central nervous system compartment that drives the motor movements of swimming tunicate larvae. We found that the expression patterns of important regulators of MG neuron subtype specification are highly conserved during the development of the non-swimming larvae of M. occulta, suggesting that the gene networks regulating their expression are largely intact in this species, despite the loss of swimming ability. However, we identified a M. occulta-specific reduction in expression of the important motor neuron terminal selector gene Ebf (Collier/Olf/EBF or COE) in the Motor Ganglion. Although M. occulta Ebf is predicted to encode a fully functional protein, its expression was reduced in developing motor neurons when compared to species with swimming larvae, which was corroborated by measuring allele-specific expression of Ebf in interspecific hybrid embryos produced by crossing M. occulta with the closely related swimming species M. oculata. Comparative reporter construct experiments also revealed a specific cis-regulatory sequence change that underlies the reduced expression of M. occulta Ebf in motor neurons, but not in other tissues and cell types. This points to a potential mechanism for arresting larval motor neuron differentiation in the non-swimming larvae of this species.

evolutionary biology↗